Since the first report of the successful use of a monoclonal antibody for the treatment of human B cell lymphoma in 1982, several antibodies have become incorporated into standard treatment protocols for cancer. One of the most important factors that determine antibody activity in vivo is the efficient interaction with cellular Fc-receptors on innate immune effector cells. It has become clear that the outcome of this interaction is influenced by several factors, such as the antibody isotype-specific affinity to activating and inhibitory receptors, the level of inhibitory FcgammaRIIB expression, and the composition of the sugar side chain attached to the antibody Fc-portion. These novel insights into antibody FcR interactions might be useful to produce the next generation of improved immunotherapeutic molecules.